title: Brain creatine elevation and N-Acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of neuroAIDS.
abstract: Proton magnetic resonance spectroscopy has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate and N-Acetylaspartate/creatine are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed, proton magnetic resonance spectroscopy revealed a decrease in N-Acetylaspartate, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia.
authors.affiliation: Neuroradiology Division, Department of Radiology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Annamalai
authors.forename: Tricia
authors.initials: T
authors.lastname: Burdo
authors.forename: Chan-Gyu
authors.initials: CG
authors.lastname: Joo
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Bombardier
authors.forename: Robert
authors.initials: R
authors.lastname: Fell
authors.forename: Reza
authors.initials: R
authors.lastname: Hakimelahi
authors.forename: Julian
authors.initials: J
authors.lastname: He
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Campbell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Curran
authors.forename: Elkan F
authors.initials: EF
authors.lastname: Halpern
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
authors.forename: R Gilberto
authors.initials: RG
authors.lastname: González
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism*; D004734:Energy Metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007294:Inositol / Q000378:metabolism; D008251:Macaca; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology; D019562:Viral Load
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline